<p>Achieving functional tissue regeneration hinges on the coordinated growth of intricate blood vessels and nerves within the defect area. However, current strategies do not offer a reliable and effective way to fulfill this critical need. To address this challenge, a three-dimensional (3D) gelatin methacryloyl–multi-walled carbon nanotube/cobalt (GelMA–MWCNTs/Co) hydrogel with controlled release of cobalt (Co) ions was developed for hypoxia-mimicking and dual beneficial effects on promoting vasculogenesis and neurogenesis. GelMA–MWCNTs/Co hydrogel exhibited sustained release of Co ions, promoting laden cell viability and long-term cell survival. GelMA–MWCNTs/Co hydrogel effectively enhanced human umbilical vein endothelial cells (HUVECs) vasculogenesis when cocultured with stem cells from apical papilla (SCAP). Moreover, this hydrogel facilitated the interaction between the pre-formed vascular and neural-like structures generated by electrical stimulation-induced SCAP (iSCAP). Furthermore, our in vivo study revealed that the GelMA–MWCNTs/Co hydrogel remarkably enhanced neovascularization and accelerated anastomosis with the host vasculature. The pre-vascularized scaffolds boosted the presence of neural differentiated SCAP in the regenerated tissue. This study provided proof of integrating functional Co ions release materials and dental-derived stem cells within a hydrogel scaffold as a promising potential for achieving simultaneous vascularization and neurogenesis.</p> Graphical abstract <p></p>

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Functional cobalt-doped hydrogel scaffold enhances concurrent vascularization and neurogenesis

  • Junqing Liu,
  • Jun Kang,
  • Ting Zou,
  • Mingxin Hu,
  • Yuchen Zhang,
  • Shulan Lin,
  • Ye Liang,
  • Jialin Zhong,
  • Yi Zhao,
  • Xi Wei,
  • Chengfei Zhang

摘要

Achieving functional tissue regeneration hinges on the coordinated growth of intricate blood vessels and nerves within the defect area. However, current strategies do not offer a reliable and effective way to fulfill this critical need. To address this challenge, a three-dimensional (3D) gelatin methacryloyl–multi-walled carbon nanotube/cobalt (GelMA–MWCNTs/Co) hydrogel with controlled release of cobalt (Co) ions was developed for hypoxia-mimicking and dual beneficial effects on promoting vasculogenesis and neurogenesis. GelMA–MWCNTs/Co hydrogel exhibited sustained release of Co ions, promoting laden cell viability and long-term cell survival. GelMA–MWCNTs/Co hydrogel effectively enhanced human umbilical vein endothelial cells (HUVECs) vasculogenesis when cocultured with stem cells from apical papilla (SCAP). Moreover, this hydrogel facilitated the interaction between the pre-formed vascular and neural-like structures generated by electrical stimulation-induced SCAP (iSCAP). Furthermore, our in vivo study revealed that the GelMA–MWCNTs/Co hydrogel remarkably enhanced neovascularization and accelerated anastomosis with the host vasculature. The pre-vascularized scaffolds boosted the presence of neural differentiated SCAP in the regenerated tissue. This study provided proof of integrating functional Co ions release materials and dental-derived stem cells within a hydrogel scaffold as a promising potential for achieving simultaneous vascularization and neurogenesis.

Graphical abstract